Variant chr8-143718828-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139021.3(MAPK15):c.340G>A(p.Val114Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000683 in 1,610,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000093 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

MAPK15
NM_139021.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

Variant links:

Genes affected

MAPK15 (HGNC:24667): (mitogen-activated protein kinase 15) Enables MAP kinase activity and chromatin binding activity. Involved in several processes, including dopamine uptake; positive regulation of DNA metabolic process; and regulation of organelle organization. Located in several cellular components, including Golgi apparatus; autophagosome; and microtubule organizing center. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

MAPK15 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10748705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK15	NM_139021.3 linkuse as main transcript	c.340G>A	p.Val114Met	missense_variant	5/14	ENST00000338033.9	NP_620590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK15	ENST00000338033.9 linkuse as main transcript	c.340G>A	p.Val114Met	missense_variant	5/14	1	NM_139021.3	ENSP00000337691	P1	Q8TD08-1
	ENST00000527908.1 linkuse as main transcript	n.64C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.0000862

AC:

AN:

150772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000667

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000612

AC:

AN:

244900

Hom.:

AF XY:

0.0000749

AC XY:

AN XY:

133560

show subpopulations

Gnomad AFR exome

AF:

0.000513

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000365

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000658

AC:

AN:

1459612

Hom.:

Cov.:

AF XY:

0.0000689

AC XY:

AN XY:

726014

show subpopulations

Gnomad4 AFR exome

AF:

0.000927

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.0000928

AC:

AN:

150890

Hom.:

Cov.:

AF XY:

0.0000950

AC XY:

AN XY:

73690

show subpopulations

Gnomad4 AFR

AF:

0.000219

Gnomad4 AMR

AF:

0.0000666

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000763

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000660

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.340G>A (p.V114M) alteration is located in exon 5 (coding exon 5) of the MAPK15 gene. This alteration results from a G to A substitution at nucleotide position 340, causing the valine (V) at amino acid position 114 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.033

T;.;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.075

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

M;.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.80

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.066

T;T;T

Sift4G

Benign

0.061

T;T;T

Polyphen

0.037

B;.;.

Vest4

0.41

MVP

0.57

MPC

0.11

ClinPred

0.035

GERP RS

1.9

Varity_R

0.025

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over